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Universal physical responses to stretch in the living cell

Abstract

With every beat of the heart, inflation of the lung or peristalsis of the gut, cell types of diverse function are subjected to substantial stretch. Stretch is a potent stimulus for growth, differentiation, migration, remodelling and gene expression1,2. Here, we report that in response to transient stretch the cytoskeleton fluidizes in such a way as to define a universal response class. This finding implicates mechanisms mediated not only by specific signalling intermediates, as is usually assumed, but also by non-specific actions of a slowly evolving network of physical forces. These results support the idea that the cell interior is at once a crowded chemical space3 and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws. These laws seem to be both universal and primitive, and thus comprise a striking intersection between the worlds of cell biology and soft matter physics.

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Figure 1: A single transient stretch drives fractional stiffness G′ n down and the phase angle δ up, indicating fluidization of the cytoskeleton.
Figure 2: A broad variety of cell systems were fluidized by a transient stretch of 10% amplitude.
Figure 3: Two unifying relationships describe the response to stretch of a broad variety of cell systems.
Figure 4: Structural relaxation takes place on timescales that grow with the time elapsed since the application of stretch and is slower than any exponential process.

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Acknowledgements

These studies were supported by grants from National Institutes of Health and from the Spanish Ministries of Education and Science and Health. We thank R. Panettieri for providing cells, and R. Farré, D. Fletcher, F. Ritort and V. Viasnoff for discussions.

Author Contributions X.T. and J.J.F. designed research and wrote the manuscript. J.P.B. conducted the theoretical analysis. X.T. and D.N. designed and implemented the experimental system. X.T., L.D. and S.S.A. optimized experimental conditions and treatments. W.T.G. and D.J.T. helped to design experimental protocols and interpret data. D.J.T. provided cells and reagents. X.T. performed all stretch experiments and data analysis. J.J.F. oversaw the project.

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Correspondence to Jeffrey J. Fredberg.

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Trepat, X., Deng, L., An, S. et al. Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007). https://doi.org/10.1038/nature05824

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